The clinical data, diagnose and treatment of a child with familial glucocorticoid deficiency (FGD) caused by the NNT gene mutation who was treated in the Department of Endocrinology, Children′s Hospital Affiliated to Nanjing Medical University in November 2014 were retrospectively analyzed.The female child with 1 year and 5 months old presented with 6 months of skin pigmentation.Laboratory examinations showed decreased cortisol and increased adrenocorticotropic hormone.During the follow-up period, she developed convulsions and precocious puberty.Whole exome sequencing revealed that the patient carried a homozygous mutation c. 1054G > A (p.G352R) in exon 8 of the NNT gene, which was a newly reported gene mutation.Domestic cases of FGD caused by the NNT gene mutation has never been reported yet.Through literature review of a total of 40 reported children with FGD caused by the NNT gene mutation, typical manifestations included skin pigmentation, hypoglycemia and seizures, alongside mineralocorticoid deficiency, precious puberty, abnormal male gonadal development, thyroid diseases and heart diseases.

The clinical data, diagnosis and treatment of a child with Robinow syndrome (RS) caused by the DVL1 gene mutation, who was treated in the Department of Endocrinology, Genetics and Metabolism, Children′s Hospital of Nanjing Medical University in May 2023, were retrospectively analyzed.The male child, 2 years old, presented with 2 years of external genital abnormality.The main clinical features included intrauterine growth retardation, external genital abnormalities, craniofacial anomalies, skeletal malformations and congenital heart diseases.Whole exome sequencing revealed that the patient carried a heterozygous mutation c. 1529delG(p.G510Vfs*139) in exon 14 of the DVL1 gene.Cases of the DVL1 gene mutation have not been documented in Chinese.A review of literature identified 25 (including the case in this report) cases of RS in children attributed to DVL1 gene mutations, revealing common clinical features such as craniofacial anomalies, skeletal malformations, external genital abnormalities, heart diseases, short stature, and hearing impairments.Cognitive abilities are typically unaffected, and reproductive function remains normal.Notably, 19 identified DVL1 gene mutations are clustered within a specific genomic region (c.1496-c.1631), with no discernible genotype-phenotype correlation observed.

Objective:To investigate the effects of compound Duzhong Jiangu Granules on joint function and gut microbiota in patients with Kashin-Beck disease.Methods:A single group pre- and post-experimental design was conducted, the patients with Kashin-Beck disease were selected as the subjects in Xunyi County, Xianyang City, Shaanxi Province; and treated with oral administration of compound Duzhong Jiangu Granules (12 g/bag, 1 bag/time, 3 times/day) for a period of 1 month. The improvement of joint function was evaluated using the joint dysfunction index scoring method before and after treatment. Morning stool samples of patients were collected and the changes in gut microbiota were analyzed before and after treatment using 16S rDNA sequencing technology.Results:A total of 87 patients with Kashin-Beck disease were included, including 44 males and 43 females; the age was (60.38 ± 7.12) years old, and the body mass index was (23.67 ± 3.59) kg/m 2. The comprehensive scores of joint dysfunction index for patients with Kashin-Beck disease before and after treatment were (7.27 ± 2.05) and (5.86 ± 2.01) points, respectively, and the difference was statistically significant ( t = 5.88, P < 0.001). The sequencing results of gut microbiota showed that there were statistically significant differences in the alpha diversity (chao1, observed species index) and beta diversity of gut microbiota in patients with Kashin-Beck disease before and after treatment ( Z = - 5.08, - 5.03, R = 0.09, P < 0.001). In the distribution of gut microbiota, Firmicutes was the dominant phylum, with relative abundances of 50.21% and 52.09% before and after treatment, respectively; the Bifidobacterium was the dominant bacterial genus, with relative abundances of 16.83% and 18.81% before and after treatment, respectively. At the genus level, a total of 17 gut microbiota genera were screened out, among which the relative abundances of Hafnia-Obesumbacterium, Gammaproteobacteria_unclassified, Acinetobacter, Pantoea, Leuconostoc, and Akkermanisia were significantly higher than before treatment ( Z = - 2.40, - 2.24, - 2.06, - 3.59, - 2.24, - 2.11, P < 0.05). The relative abundances of Dubosiella, Selenomonas, Anaeroplasma, Lachnospiraceae_ NK4A136_group, Rikenella, Prevotella, Megasphaera, Lactobacillus, Prevotella-9, Phascolarctobacterium, and Desulfovibrio were significantly lower than before treatment ( Z = - 9.38, - 2.61, - 2.18, - 8.43, - 2.45, - 2.46, - 2.49, - 7.29, - 2.29, - 2.55, - 2.08, P < 0.05). Conclusions:Compound Duzhong Jiangu Granules can effectively improve the joint function of patients with Kashin-Beck disease, and alter the diversity and richness of the gut microbiota community. It may reduce clinical symptoms in patients by regulating the structure of gut microbiota.